Department of Hepatobiliary Surgery, Zhongshan Hospital Xiamen University, Xiamen, China.
Department of Internal Medicine, Siming Branch, The First Affiliated Hospital of Xiamen University, Xiamen, China.
J Cell Physiol. 2019 Nov;234(11):20342-20353. doi: 10.1002/jcp.28634. Epub 2019 Apr 8.
The prognosis of hepatocellular carcinoma (HCC) after R0 resection is unsatisfactory due to the high rate of recurrence. In this study, we investigated the recurrence-related RNAs and the underlying mechanism. The long noncoding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) expression data and clinical information of 247 patients who underwent R0 resection patients with HCC were obtained from The Cancer Genome Atlas. Comparing the 1-year recurrence group (n = 56) with the nonrecurrence group (n = 60), we detected 34 differentially expressed lncRNAs (DElncRNAs), five DEmiRNAs, and 216 DEmRNAs. Of these, three DElncRNAs, hsa-mir-150-5p, and 11 DEmRNAs were selected for constructing the competing endogenous RNA (ceRNA) network. Next, two nomogram models were constructed based separately on the lncRNAs and mRNAs that were further selected by Cox and least absolute shrinkage and selection operator regression analysis. The two nomogram models that showed a high prediction accuracy for disease-free survival with the concordance indexes at 0.725 and 0.639. Further functional enrichment analysis of DEmRNAs showed that the mRNAs in the ceRNA network and nomogram models were associated with immune pathways. Hence, we constructed a hsa-mir-150-5p-centric ceRNA network and two effective nomogram prognostic models, and the related RNAs may be useful as potential biomarkers for predicting recurrence in patients with HCC.
由于 HCC 复发率高,R0 切除术后 HCC 的预后仍不理想。本研究旨在探讨与复发相关的 RNA 及其潜在机制。从癌症基因组图谱中获取了 247 例接受 HCC R0 切除术患者的长链非编码 RNA(lncRNA)、微小 RNA(miRNA)和信使 RNA(mRNA)表达数据及临床资料。将 1 年复发组(n=56)与非复发组(n=60)进行比较,检测到 34 个差异表达的 lncRNA(DElncRNA)、5 个差异表达的 miRNA 和 216 个差异表达的 mRNA。其中,选取了 3 个 DElncRNA、hsa-mir-150-5p 和 11 个 DEmRNA 构建竞争性内源性 RNA(ceRNA)网络。进一步通过 Cox 和最小绝对收缩和选择算子回归分析对 lncRNA 和 mRNA 进行筛选,分别构建了两个列线图模型。两个列线图模型的疾病无进展生存率预测准确性较高,一致性指数分别为 0.725 和 0.639。对 DEmRNA 的进一步功能富集分析表明,ceRNA 网络和列线图模型中的 mRNAs 与免疫途径相关。因此,我们构建了一个 hsa-mir-150-5p 为中心的 ceRNA 网络和两个有效的列线图预后模型,相关 RNA 可能作为预测 HCC 患者复发的潜在生物标志物。